3 de julio de 2016

Lurasidone



Lurasidone is FDA approved for the treatment of schizophrenia since 2010[3] and depressive episodes associated with bipolar I disorder since 2013. It received regulatory approval in the UK in September 2014. In October 2014, NHS Scotland advised use of lurasidone for schizophrenic adults who have not seen improvements with previous antipsychotics due to problems that arise from weight gain or changes in metabolic pathways when taking other medications. It received EMA approval on January 24, 2014. It was launched in Canada for the treatment of schizophrenia in September 2012, Health Canada giving their Summary Basis of Decision (SBD) as favourable on October 15, 2012.European Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults. It is approved for use in the EU.

In July 2013 lurasidone received approval for bipolar I depression. Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions being quetiapine, olanzapine and possibly asenapine) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significant antimanic activity, which is yet to be clearly demonstrated for lurasidone.

Lurasidone may be useful for treating the cognitive and memory deficits seen in schizophrenia. In animal studies, it reversed dizocilpine-induced learning and memory impairment and was found to be superior in doing this to all of the other antipsychotics examined, including risperidone, olanzapine, quetiapine, clozapine, aripiprazole, and haloperidol.
Lurasidone has activity at several serotonin receptors that are involved in learning and memory, and unlike most other antipsychotics, lacks any anticholinergic effects (which are known to impair cognitive processes and memory). These properties may underlie its improved effectiveness in treating these symptoms relative to older agents.

Lurasidone has completed phase III clinical trial for extended use study in India,  although it is not yet approved in India.

Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.
Contraindications

Lurasidone is contraindicated in individuals who are taking strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, levodropropizine, etc.) or inducers (carbamazepine, St. John's wort, phenytoin, rifampicin etc.).[22] The use of lurasidone in pregnant women has not been studied and is not recommended, although it should be noted that it is a category B drug.[23] Excretion in breast milk is also unknown; lurasidone is not recommended for breastfeeding women.[24] In the United States it is not indicated for use in children.
Adverse effects
See also: List of adverse effects of lurasidone

Side effects are generally similar to other antipsychotics. The drug has a relatively well-tolerated side effect profile, with low propensity for QTc interval changes, weight and lipid-related adverse effects. In a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs it was found to produce the second least (after haloperidol) weight gain, the least QT interval prolongation, the fourth most extrapyramidal side effects (after haloperidol, zotepine and chlorpromazine) and the sixth least sedation (after paliperidone, sertindole, amisulpride, iloperidone and aripiprazole).

As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for a stroke or transient ischemic attack;[28][29] however, these risks are not likely to be greater than those associated with antipsychotics of other classes.[30] Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with antipsychotic use.
Pharmacology
Mechanism of action

Lurasidone acts as an antagonist of the following sites:

    α1-adrenergic receptor (Ki = 48 nM)
    α2A-adrenergic receptor (Ki = 1.6 nM)
    α2C-adrenergic receptor (Ki = 10.8 nM)
    D1 receptor (Ki = 262 nM)
    D2 receptor (Ki = 1.7 nM)
    5-HT2A receptor (Ki = 2.0 nM)
    5-HT2C receptor (Ki = 415 nM)
    5-HT7 receptor (Ki = 0.5 nM)

And as a partial agonist of the following sites:

    5-HT1A receptor (Ki = 6.8 nM)

Lurasidone has negligible actions at the H1 and mACh receptors.
Pharmacokinetics

Studies have shown that when lurasidone is taken with food, absorption increases.

Lurasidone is metabolized in the liver via the enzyme CYP3A4.[28] This means that its plasma concentrations may be increased when combined with CYP3A4 inhibitors like ketoconazole or grapefruit juice, possibly leading to more side effects. Co-administration of CYP3A4 inducers like rifampicin or St. John's wort can reduce plasma levels and consequently decrease the effects of the drug.
References

"PRODUCT INFORMATION LATUDA (lurasidone hydrochloride)" (PDF). TGA eBusiness Services. Therapeutic Goods Administration. 16 April 2014. Retrieved 1 May 2014.
Meyer, Jonathan M; Loebel, Antony D; Schweizer, Edward (2009). "Lurasidone: A new drug in development for schizophrenia". Expert Opinion on Investigational Drugs 18 (11): 1715–26. doi:10.1517/13543780903286388. PMID 19780705.
"FDA approves Latuda to treat schizophrenia in adults" (Press release). USFDA. 2010-10-28. Retrieved October 29, 2010.
Lowes R. Lurasidone Approved for Bipolar Depression [Internet]. Medscape. 2013 [cited 2013 Oct 2]. Available from: http://www.medscape.com/viewarticle/807204
"Lurasidone, 18.5mg, 37mg, 74mg film-coated tablets (Latuda) SMC No. (994/14)" (PDF). Scottish Medicines Consortium. 2014.
"Summary Basis of Decision (SBD) for Latuda". Health Canada. 2012.
"European Marketing Authorization for Latuda". takeda.com. Retrieved 25 November 2015.
"European Medicines Agency - Find medicine - Latuda". europa.eu. Retrieved 25 November 2015.
Young, Allan H.; McElroy, Susan L.; Bauer, Michael; Philips, Nabil; Chang, William; Olausson, Bengt; Paulsson, Björn; Brecher, Martin; EMBOLDEN I (Trial 001) Investigators (2010). "A Double-Blind, Placebo-Controlled Study of Quetiapine and Lithium Monotherapy in Adults in the Acute Phase of Bipolar Depression (EMBOLDEN I)". The Journal of Clinical Psychiatry 71 (2): 150–62. doi:10.4088/JCP.08m04995gre. PMID 20122369.
Suppes, Trisha; Datto, Catherine; Minkwitz, Margaret; Nordenhem, Arvid; Walker, Chris; Darko, Denis (2010). "Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression". Journal of Affective Disorders 121 (1–2): 106–15. doi:10.1016/j.jad.2009.10.007. PMID 19903574.
"Corrigendum". Bipolar Disorders 10 (3): 451. 2008. doi:10.1111/j.1399-5618.2008.00585.x.
Thase, ME (2008). "Quetiapine monotherapy for bipolar depression". Neuropsychiatric disease and treatment 4 (1): 11–21. doi:10.2147/ndt.s1162. PMC 2515925. PMID 18728771.
Tohen, Mauricio; Vieta, E; Calabrese, J; Ketter, TA; Sachs, G; Bowden, C; Mitchell, PB; Centorrino, F; Risser, R; Baker, RW; Evans, AR; Beymer, K; Dube, S; Tollefson, GD; Breier, A (2003). "Efficacy of Olanzapine and Olanzapine-Fluoxetine Combination in the Treatment of Bipolar I Depression". Archives of General Psychiatry 60 (11): 1079–88. doi:10.1001/archpsyc.60.11.1079. PMID 14609883.
Tohen, M.; Katagiri, H.; Fujikoshi, S.; Kanba, S. (2013). "Efficacy of olanzapine monotherapy in acute bipolar depression: A pooled analysis of controlled studies". Journal of Affective Disorders 149 (1–3): 196–201. doi:10.1016/j.jad.2013.01.022. PMID 23485111.
Corya, Sara A.; Perlis, Roy H.; Keck Jr, Paul E.; Lin, Daniel Y.; Case, Michael G.; Williamson, Doug J.; Tohen, Mauricio F. (2006). "A 24-Week Open-Label Extension Study of Olanzapine-Fluoxetine Combination and Olanzapine Monotherapy in the Treatment of Bipolar Depression". The Journal of Clinical Psychiatry 67 (5): 798–806. doi:10.4088/JCP.v67n0514. PMID 16841630.